Oncotarget

Research Papers:

Characterization of iPS87, a prostate cancer stem cell-like cell line

Erika N. Assoun _, April N. Meyer, Maggie Y. Jiang, Stephen M. Baird, Martin Haas and Daniel J. Donoghue

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Oncotarget. 2020; 11:1075-1084. https://doi.org/10.18632/oncotarget.27524

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Abstract

Erika N. Assoun1, April N. Meyer2, Maggie Y. Jiang1, Stephen M. Baird3, Martin Haas4 and Daniel J. Donoghue2,4

1 Division of Biological Sciences, University of California San Diego, La Jolla, San Diego, CA 92093, USA

2 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, San Diego, CA 92093, USA

3 Department of Pathology, University of California San Diego, La Jolla, San Diego, CA 92093, USA

4 Moores UCSD Cancer Center, University of California San Diego, La Jolla, San Diego, CA 92093, USA

Correspondence to:

Daniel J. Donoghue,email: ddonoghue@ucsd.edu

Keywords: prostate cancer; stem cells; androgen independent; androgen deprivation therapy; castration resistant prostate cancer

Received: October 31, 2019     Accepted: March 03, 2020     Published: March 24, 2020

ABSTRACT

Prostate cancer affects hundreds of thousands of men and families throughout the world. Although chemotherapy, radiation, surgery, and androgen deprivation therapy are applied, these therapies do not cure metastatic prostate cancer. Patients treated by androgen deprivation often develop castration resistant prostate cancer which is incurable. Novel approaches of treatment are clearly necessary.

We have previously shown that prostate cancer originates as a stem cell disease. A prostate cancer patient sample, #87, obtained from prostatectomy surgery, was collected and frozen as single cell suspension. Cancer stem cell cultures were grown, single cell-cloned, and shown to be tumorigenic in SCID mice. However, outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio. Tumor-inducing activity could be restored by inducing the cells to pluripotency using the method of Yamanaka. Cultures of human prostate-derived normal epithelial cells acquired from commercial sources were similarly induced to pluripotency and these did not acquire a tumor phenotype in vivo. To characterize the iPS87 cell line, cells were stained with antibodies to various markers of stem cells including: ALDH7A1, LGR5, Oct4, Nanog, Sox2, Androgen Receptor, and Retinoid X Receptor. These markers were found to be expressed by iPS87 cells, and the high tumorigenicity in SCID mice of iPS87 was confirmed by histopathology. This research thus characterizes the iPS87 cell line as a cancer-inducing, stem cell-like cell line, which can be used in the development of novel treatments for prostate cancer.


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